The cell block (CB) offers many advantages over other cytological preparations, particularly for immunocytochemical and molecular testing. However, inconsistent cellularity remains the most common reason for dissatisfaction among cytopathologists. In recent years, there has been a surge in the demand for CBs imposed by the increasing number of minimally invasive procedures performed to obtain material for diagnostic, prognostic and predictive purposes from advanced stage cancer patients. However, routine preparation of CBs significantly increases laboratory work load, operating cost and sample turn‐around time. The objectives of our review were to: (a) identify scenarios where a CB is likely to improve diagnostic yield; (b) optimise CB preparatory methods; and (c) understand the factors influencing the success and validity of ancillary testing on various types of CBs. We performed an extensive literature search on CBs in cytology on internet search engines using the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. New CB methods, improvisations of previous CB methods, their utility for diagnosis, immunocytochemistry and molecular testing, and role in predictive biomarker testing are discussed in this review. CBs of good quality and cellularity outperform other cytology preparations in their reliability and versatility for ancillary testing. With many CB methods described in the literature, each with specific advantages and limitations, laboratories may choose to use one or more of the methods depending upon their infrastructure, expertise and workload.