Convergent molecular evolution, especially among distantly related species, is a hallmark of adaptation, yet the drivers of such convergence (or lack thereof) are typically unknown. Variation in molecular convergence may stem from constraints on evolutionary trajectories, such as how intramolecular epistasis and broader scale interactions among genes differ across lineages. While substantial progress has been made in understanding the prevalence of epistasis for fitness-related phenotypes, particularly in microbial systems, empirical tests of the role of epistasis in convergent molecular evolution are rare, especially in metazoans. A key obstacle is the lack of tractable, highly replicated systems to investigate the extent and generality in the causes of molecular convergence. To meet this need, we have been studying a diverse group of insects which have adapted to cardenolides, a class of steroidal plant toxins that disrupts the biomedically-relevant animal protein, Na/K-ATPase. We recently documented a remarkable 30 independent origins of cardenolide-specialization in insects, spanning 350 million years of evolution (in six taxonomic orders, spanning beetles and flies to grasshoppers). Although a handful of substitutions did indeed convergently evolve in all orders, some species lack these substitutions and others have taken alternative paths. Our findings, which also show distinct patterns among groups (e.g., Coleoptera vs. Lepidoptera, each with multiple origins) suggests lineage-specific constraints of genomic background. This group of insects thus presents a treasure trove of opportunity to decipher the drivers of molecular convergence. How variable are the epistatic interactions between lineages, and do these differences drive alternative outcomes in molecular evolution? Do multiple genes coevolve, shaping patterns of convergence? For example, have ABC transporter genes involved in excretion and storage, which complement resistance to cardenolides, evolved in