Microscopes often represent a significant investment of funds and are sophisticated optical instruments that require periodic maintenance and cleaning to guarantee successful microscopy and perfect images. When neglected, exposure to dust, lint, pollen, dirt, and failure to remove immersion oil in a timely manner can seriously damage optical performance. Over the years, a variety of cleaning procedures have been recommended, but many users remain unsure as to which of these will yield the best results. The choice of the best cleaning method depends on the nature of the optical surface and the type of substance to be removed.

A microscope that remains unused for a long period of time can accumulate dust and debris from the air, which can lead to deterioration of image quality even though the instrument may be practically new. Even when carefully covered for protection during periods of inactivity, however, microscopes that are used regularly are subject to build up of contaminants. Some of these are unavoidably introduced from the environment and others by the microscopists themselves, especially in areas where the hands, eyelashes, and even moisture from breathing contact the instrument over time. The critical areas include:
- The external surface of the front lens of the objective
- The surface of the camera sensor and its protective glass cover
- Both surfaces of the cover slip
- The surface of the microscope slide
- The surface of the camera adapter optics
- Surface of the upper lens of the condenser
- The outer and inner surfaces of the eyepiece as well as the upper surface of the reticule
- The outer surface of any protective glass covering openings through which light exits
- Other glass surfaces in the light path such as halogen lamps, high pressure arc-discharge lamps, fluorescence filters and beam splitters, collector lenses, or contrast and heat filters
Some optical surfaces are more sensitive to dirt than others. The front lens of the objective is particularly significant, as when the optical elements at or near the conjugate field (image) planes are dirty, damaged, or defective, artifacts are likely to appear in sharp focus superimposed on the specimen image (see Figure 2). Ironically, the higher the quality of optical components, such as the condenser and collecting and relay lenses, the more these blemishes interfere and contribute to optical noise. Before every critical use, check the front lens of the objective for dirt.
For any dry objective, the smaller the free working distance and the smaller the surface area of the concave front lens, the greater the danger of soiling the front lens with embedding media, immersion liquids, or dust. The front lens of an immersion objective should be cleaned to remove residue both after use and before applying fresh immersion liquid. The mixing of different immersion media, as well as different lots of the same medium can result in blurred images. Though the utilization of immersion oil is essential in maximizing microscope optical performance, its improper use or the failure to immediately remove the oil after each use constitutes the most serious contaminant that must be dealt with in instrument maintenance, and thus will be discussed in further detail in a later section.

Microscopes that are equipped with digital cameras may develop a degradation in captured image quality or exhibit image artifacts caused by accumulation of contamination either on filter elements that are sometimes utilized in the camera adapter or on the optical glass window that may be incorporated to seal the camera housing and protect the charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS) image sensor. In practice, if dark specks or similar in-focus artifacts are observed in digital images, and they are not in the specimen plane, their most likely cause is particulate contamination on the image sensor or an associated filter surface. The cameras always need to be handled with the utmost care and protected from dirt according to the manufacturer's recommendations.