The 14-3-3 (YWHA or Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation proteins) are a family of highly conserved, homologous proteins critical to diverse cellular events including cell cycle, signal transduction and embryonic development. Various species-specific isoforms of 14-3-3 exist, encoded by separate genes. They are expressed in a wide variety of organisms ranging from plants to animals, including the fruit fly or Drosophila melanogaster. Drosophila is one of the most universally accepted model systems to study complex cellular mechanisms of signalling and development. However, regulation of these processes in fruit flies by the 14-3-3 proteins have not been entirely understood. This mini review encapsulates the expression, distribution, interactions and regulatory roles of the 14-3-3 proteins in Drosophila. The analysis would help to elucidate some of the molecular bases of key cell-signalling mechanisms and development.