Whole genome duplications (WGDs) followed by diploidization, which includes gene loss, have been an important recurrent process in the evolution of higher eukaryotes. Gene retention is biased to specific functional gene categories during diploidization. Dosage-sensitive genes, which include transcription factors, are significantly over-retained following WGDs. By contrast, these same functional gene categories exhibit lower retention rates following smaller scale duplications (e.g., local and tandem duplicates, segmental duplicates, aneuploidy). In light of these recent observations, we review current theories that address the fate of nuclear genes following duplication events (i.e., Gain of Function Hypothesis, Subfunctionalization Hypothesis, Increased Gene Dosage Hypothesis, Functional Buffering Model, and the Gene Balance Hypothesis). We broadly review different mechanisms of dosage-compensation that have evolved to alleviate harmful dosage-imbalances. In addition, we examine a recently proposed extension of the Gene Balance Hypothesis to explain the shared single copy status for a specific functional class of genes across the flowering plants. We speculate that the preferential retention of dosage-sensitive genes (e.g., regulatory genes such as transcription factors) and gene loss following WGDs has played a significant role in the development of morphological complexity in eukaryotes and facilitating speciation, respectively. Lastly, we will review recent findings that suggest polyploid lineages had increased rates of survival and speciation following mass extinction events, including the Cretaceous-Tertiary (KT) extinction.