The 14-3-3 (YWHA or Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation proteins) are a family of abundant, highly conserved, ubiquitous, acidic, and homologous proteins expressed in most eukaryotes ranging from plants to animals, including humans, important in regulating a multitude of cellular processes such as signal transduction, cell cycle, protein trafficking, metabolism, apoptosis, and development. Mammals have been noted contain seven isoforms of these proteins (beta, epsilon, eta, gamma, sigma, tau/theta, and zeta), encoded by separate genes. The 14-3-3 proteins are known to interact with over 200 binding partners in isoform-specific, tissue-specific, and developmental stage-specific ways. The present review article encapsulates previously published research articles that report 14-3-3-interactors, and investigates isoform-specific interactions within a wide array of mammalian species, cells, tissues, organs, and developmental stages. Of the hundreds of binding partners of 14-3-3 discovered till date, this paper focuses on analyzing selected, representative interactors with key functional roles. The study would help a better understanding of isoform-specific interactions of this critical protein family in mammals