Thousands of common genetic variants in the human population have been associated with disease risk and phenotypic variation by genome-wide association studies (GWAS). However, the majority of GWAS variants fall into noncoding regions of the genome, complicating our understanding of their regulatory functions, and few molecular mechanisms of GWAS variant effects have been clearly elucidated. Here, we set out to review genetic variant effects, focusing on expression quantitative trait loci (eQTLs), including their utility in interpreting GWAS variant mechanisms. We discuss the interrelated challenges and opportunities for eQTL analysis, covering determining causal variants, elucidating molecular mechanisms of action, and understanding context variability. Addressing these questions can enable better functional characterization of disease-associated loci and provide insights into fundamental biological questions of the noncoding genetic regulatory code and its control of gene expression.