The American Tropics, more popularly referred to as the “Neotropics”, is the most biodiverse region in the world. For decades, scientists have introduced countless speciation hypotheses in an attempt to address how and why this region is so species rich. Despite these attempts, the origins and persistence of this biodiversity remain a mystery. In this review, we identify the main diversification modes at play and comprehensively revisit and explore these long-standing diversification hypotheses in the American Tropics. Not only do we look at their origins and how they have progressed over the years, but we also offer additional perspective by compiling a large meta-analysis of over 2,000 publications, which we narrowed to almost 500 publications, to reveal underlying patterns in distribution and coverage across taxonomic groups, biogeographical regions, and drivers of diversification within the major hypotheses. We emphasize the crucial need to revisit our scientific understanding of this biodiversity’s hotspots complex history and the ultra-diversity that persists to this day.