Definitive cytopathological interpretation of some of the effusion fluids may not be possible based on cytomorphological evaluation alone. As discussed in other reviews, this is due to various reasons specifically applicable to effusion fluids including remarkably wide morphologic spectrum of reactive mesothelial cells overlapping with some well to moderately differentiated metastatic carcinoma. The challenge is subject to various factors including level of interpreter training or experience, institutional demographics (such as type of prevalent diseases, predominant sex and age group), technical advances in ancillary support, and expertise in cytopreparatory processing. In such cases immunohistochemistry performed on cell-block sections is simple objective adjunct with or without other ancillary techniques. Ongoing increase in number of immunomarkers along with rabbit monoclonal antibodies with relatively higher affinity is further refining this field. SCIP (subtractive coordinate immunoreactivity pattern) approach, discussed as separate dedicated review article, facilitates refined interpretation of immunoreactivity pattern in coordinate manner on various serial sections of cell-blocks. However, many variables such as delay after specimen collection, specimen processing related factors including fixation and storage; ambient conditions under which paraffin blocks are archived (for retrospective testing); antigen retrieval method; duration of antigen retrieval step; antibody clone and dilution; and antibody application time are common with application of immunohistochemistry in other areas. This review is dedicated to highlight technical aspects including processing of effusion specimens for optimum immunocytochemical evaluation along with commonly used immunomarkers in effusion cytopathology. This review focuses on the technical and general information about various immunomarkers.