Genetic variation has multiple effects on the proteome. It may influence the expression level of proteins, modify their sequences through single nucleotide polymorphisms, the occurrence of allelic variants, or alternative splicing (ASP) events. This perspective paper summarizes the major effects of genetic variability on protein expression and isoforms and provides an overview of proteomics techniques and methods that allow studying the effects of genetic variability at different levels of the proteome. The paper provides an overview of recent quantitative trait loci studies performed to explore the effect of genetic variation on protein expression (pQTL). Finally it gives a perspective view on advances in proteomics technology and the role of the Chromosome-Centric Human Proteome Project (C-HPP) by creating large-scale resources that may facilitate performing more comprehensive pQTL experiments in the future.