The ribosome is a complex molecular machine composed of numerous distinct proteins and nucleic acids and is responsible for protein synthesis in every living cell. Ribosome biogenesis is one of the most multifaceted and energy- demanding processes in biology, involving a large number of assembly and maturation factors, the functions of which are orchestrated by multiple cellular inputs, including mitogenic signals and nutrient availability. Although causal associations between inherited mutations affecting ribosome biogenesis and elevated cancer risk have been established over the past decade, mechanistic data have emerged suggesting a broader role for dysregulated ribosome biogenesis in the development and progression of most spontaneous cancers. In this Opinion article, we highlight the most recent findings that provide new insights into the molecular basis of ribosome biogenesis in cancer and offer our perspective on how these observations present opportunities for the design of new targeted cancer treatments.