Appropriate pre-transplant immunologic evaluation is an essential pre-requisite to obtain optimal short-term and long-term graft outcomes. Policies vary widely between different institutes and states, due to lack of uniformly acceptable guidelines. Possible approach for a non-sensitized patient awaiting first renal transplant is presented here. Pooled Antigen Panel (Single Antigen Qualitative Analysis) can be used as an initial screening test followed by Single Antigen Bead Assay for semi-quantitative analysis of donor specific anti-HLA antibodies—the acceptable threshold for which can vary based on institutional/state policy. Flow Cytometry Cross Match forms the most important terminal determinant—irrespective of the prior screening tests, following which, the decision to proceed with transplant can be made, if the results of flow cross match are acceptable. Semi-quantitative results of SAB assay make it a useful test—for prognostication and tailoring of immunosuppressant’s post-transplant also. Combined use of screening tests, SAB assay on a case by case basis and flow cross match, forms the basic framework for a complete and informative immunologic assessment. Role of CDC cross match today is more controversial, with widespread availability of flow cross match—a much more sensitive assay than CDC.