Although first postulated to exist nearly 100 years ago, inhibins were only isolated in 1985 from bovine and porcine follicular fluid. Inhibin A and inhibin B (heterodimers of a common α- and differing β-subunits) act as part of a negative feedback loop to regulate synthesis of follicle stimulating hormone (FSH) by gonadotrope cells of the anterior pituitary. Inhibins modulate gonadotrope function by preventing activins (homodimers of β-subunits) from binding their receptors and activating SMAD 2/3 transcription factors. In the context of the pituitary, this mode of action ensures that inhibins control activin-induced FSH production. Over the past decade, my group has helped define the mechanisms underlying the synthesis, activation and receptor binding of inhibin and activin. Based on our understanding of these processes, we have generated highly-potent inhibin agonists and specific activin antagonists. My studies have also redefined the physiological roles of these "reproductive" molecules, with increased circulating levels of activin A promoting muscle wasting and cachexia, while loss of inhibin results in a complex metabolic phenotype. Using our detailed structural knowledge, we can now manipulate the inhibins and activins to study loss/gain of function, allowing us to identify new roles for these age old hormones.