The upflow anaerobic sludge blanket (UASB) reactor can be considered as one of the promising anaerobic wastewater treatment technologies suitable for the treatment of high-strength wastewater. In the recent period, researchers have focused on the treatment of low-strength wastewater using this technology. This review focuses on the key factors affecting the reactor performance such as hydraulic retention time (HRT), temperature, organic loading rate (OLR), pH and alkalinity, granulation, wastewater characteristics, mixing, and modification to conventional configuration. Start-up and granulation played a major role in the determination of reactor performance, and various theories have been proposed to understand the mechanism of granulation. Correlation between start-up time and OLR was found to be low, as other operating parameters might have been influencing the start-up time. Flowchart depicting the development of UASB reactor over time is included. In the present work, further development and derivatives of the UASB reactor such as static granular bed reactor (SGBR) and expanded granular sludge bed (EGSB) reactor are analyzed. The optimal conditions for UASB for treating various types of substrates was found to be HRT of 3-24 h, OLR of 1-15 kg COD/m3 /d, and operational temperature in mesophilic range (30-40°C). Analysis of various modifications that pave the way for identification of future areas of research to improve reactor performance is also presented.