Assessment of immunogenicity is a major aspect in evaluating the safety of biological therapeutic proteins. It is important to evaluate the immunogenic potential of the biologics in an appropriate fashion using clearly defined strategy and clinical trials. The studies must include the appropriate risk assessment procedures using validated methods. The immune responses against the therapeutic biologics can be studied using various methodologies. These include enzyme linked immunoassays (ELISA), surface plasmon resonance (SPR), chemiluminescence, and flowcytometry assays for binding antibodies and cell based assays for neutralizing antibodies. The immune responses to the biologics can widely vary in various cross section of the population, thus a combination of techniques are necessary to fully evaluate the immunogenic potential of the biologics. This review outlines various commonly used technology platforms, its merits and shortcomings for the evaluation of the immune responses.