Medusae (aka jellyfish) have multiphasic life cycles and a propensity to adapt to, and proliferate in, a plethora of aquatic habitats, connecting them to a number of ecological and societal issues. Now, in the midst of the genomics era, affordable next-generation sequencing (NGS) platforms coupled with publically available bioinformatics tools present the much-anticipated opportunity to explore medusa taxa as potential model systems. Genome-wide studies of medusae would provide a remarkable opportunity to address long-standing questions related to the biology, physiology, and nervous system of some of the earliest pelagic animals. Furthermore, medusae have become key targets in the exploration of marine natural products, in the development of marine biomarkers, and for their application to the biomedical and robotics fields. Presented here is a synopsis of the current state of medusa research, highlighting insights provided by multi-omics studies, as well as existing knowledge gaps, calling upon the scientific community to adopt a number of medusa taxa as model systems in forthcoming research endeavors.