MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression. They have been implicated in a broad range of biological processes, and miRNA-related genetic alterations probably underlie more human diseases than currently appreciated. Several studies have identified genetic variants in miRNA target sites that are claimed to be associated with disorders ranging from Parkinson's disease to cancer. However, careful assessment of these studies indicates that very few provide a combination of rigorous genetic and functional evidence. We therefore suggest a set of concrete recommendations to guide future investigations. Specifically, we highlight the importance of unbiased association studies and follow-up functional experiments for providing a clearer picture of the extent to which microRNA target site variations are relevant in various human diseases.