Cell competition is a process by which otherwise viable cells are actively eliminated due to the presence of more competitive cells. It is a conserved phenomenon and occurs in various developmental and experimental contexts. Competitive elimination represents a safeguard mechanism that potentiates animal development. However, the process can also be hijacked, for example, by cancer cells to promote and sustain malignancy. The elucidation of the interplay between loser and winner cells in the process of cell competition will provide new targets for the development of cancer therapeutics. An important step forward was the discovery that in established models of cell competition specific components of the evolutionarily ancient and conserved innate immune system are used to eliminate “unfit” Drosophila cells. We are continuing to refine our understanding of cell competition and working to integrate these insights into a holistic model of cell competition and tissue fitness.