The last two decades witnessed a significant advancement in the field of diluted and whole blood plasma separation. This is one of the common procedures used to diagnose, cure and treat numerous acute and chronic diseases. For this separation purpose, various types of geometries of microfluidic devices, such as T-channel, Y-channel, trifurcation, constriction–expansion, curved/bend/spiral channels, a combination of any of the two geometries, etc., are being exploited, and this is detailed in this review article. The evaluation of the performance of such devices is based on the several parameters such as separation efficiency, flow rate, hematocrits, channel dimensions, etc. Thus, the current extensive review article endeavours to understand how particular geometry influences the separation efficiency for a given hematocrit. Additionally, a comparative analysis of various geometries is presented to demonstrate the less explored geometric configuration for the diluted and whole blood plasma separation. Also, a meta-analysis has been performed to highlight which geometry serves best to give a consistent separation efficiency. This article also presents tabulated data for various geometries with necessary details required from a designer’s perspective such as channel dimensions, targeted component, studied range of hematocrit and flow rate, separation efficiency, etc. The maximum separation efficiency that can be achieved for a given hematocrits and geometry has also been plotted. The current review highlights the critical findings relevant to this field, state of the art understanding and the future challenges.