Contamination is a clearly-established problem with serious consequences in the biological laboratory. It can be divided into three main categories (physical, chemical, and biological). The most common biological encountered contaminates are bacteria, molds, yeasts, viruses, mycoplasma, as well as cross contamination by other cell lines. This review provides an overview of major critical source and control options of contaminants. The critical source of contamination is suddenly or deliberately introduction of contaminants on the desired system during the beginning up to ending of laboratory work. To overcome the challenge numerous strategies must be daily exercised such as obtaining pure and viable cells from reputable gene banks; checking the characteristics of the culture periodically, and practicing good aseptic technique, and using antibiotics routinely. In general, this paper suggested that possible to reduce or eliminate contamination frequency and seriousness by visual inspection of the culture within a few days of it becoming infected.