The pathogenesis of many reproductive traits and diseases is complex and influenced by genetic and environmental risk factors that can contribute to overlapping diseases. Advances in technology and high-throughput computing provide unparalleled opportunities to study regulation of these complex systems. Questions can be addressed on a genome-wide scale and down to single cells. However, individual genetic risk factors have small effects requiring large studies. In the last 10 years, genetic studies have demonstrated the advantages and increased power for gene discovery from combining data in large international consortia. Studies on regulation of gene expression and epigenetic signals are now following this example. Increasingly, the results of these large projects are made available in the public domain so individual studies can combine results from local data and large publicly available datasets. Our studies in endometriosis and other traits illustrate some of the opportunities and challenges in the rapidly changing field of reproductive genomics.