Anaerobic digestion (AD) is a complex process that requires strict anaerobic conditions to proceed, and depends on the coordinated activity of a microbial association to transform organic material into biogas, which is mainly composed of methane and carbon dioxide. The microbiology of AD involves several microorganism groups, each of them having their own optimum working conditions. Anaerobic treatment of organic wastes presents a number of important advantages in comparison to the classical aerobic processes, which are reviewed in this article. Within the anaerobic environment, various important parameters affect the rates of the different steps of the digestion process, namely, temperature, pH, alkalinity, and volatile fatty acids (VFAs). These parameters are assessed in another section of the article, together with the different anaerobic reactor configurations used for wastewater treatment. In general, anaerobic reactors are affected by changes in external factors, but the severity of the effects is dependent upon the type, magnitude, duration, and frequency of the sudden changes. The typical responses include a decrease in performance, accumulation of VFAs, drop in pH and alkalinity, changes in biogas production and composition, and possible sludge washout. All these effects are also discussed in the article. In addition, different techniques to upgrade the biogas formed by removing CO2, H2S, excess moisture, and trace gases (e.g., siloxanes) are summarized. Finally, the different applications of AD technology as well as the most typical full-scale anaerobic configurations currently installed are also examined.