2D electrophoresis (2-DE) is still a widely used proteomic method despite the availability of high-throughput approaches for protein identification. However, a literature survey only revealed a relatively small number of 2-DE-based studies of human blood proteome. We critically reviewed comparative 2-DE-based proteomic studies, in which groups of patients under examination involved more than ten individuals. Limitation on the number of samples is explained by the requirement to take into account the individual variation of blood proteome. The scanty amount of statistical data on quantitative variations of normal blood proteome may be one of the reasons for the poor applicability of proteomic biomarkers in clinical diagnostics.