The use of nanoparticles as platforms or vehicles for applications in nanomedicine, such as drug delivery and medical imaging, has been widely reported in the literature. A key area of potential improvement in the development and implementation of nanoparticles is the design of surface treatments to maximize residence time in the bloodstream. Major obstacles to the prolonged circulation of nanoparticles include complement activation and opsonization, both of which contribute to the removal of foreign matter from the vasculature. A greater understanding of the mechanisms through which nanoparticles interact with the complement system of innate immunity may be necessary in future endeavours to optimize nanoparticle design. The range of experimental techniques available for measuring complement interaction is presented. In particular, an in vitro hemolytic complement consumption assay called the CH(50) method is compared with alternative complement measurement techniques and cellular uptake studies in order to demonstrate its effectiveness as a quantitative evaluation of overall complement interaction. Moreover, establishing the usefulness of CH(50) results as predictors of in vivo behaviour is identified as a critical area for future research.