Maintenance of male fertility is dependent on spermatogonial stem cells (SSCs) that self-renew and generate differentiating germ cells for production of spermatozoa. SSC function is dependent on growth factors produced within the testis microenvironment plus cellular factors that regulate gene expression within SSCs and modulate responses to growth factor stimulation. Despite the importance of SSCs for male fertility, the molecular mechanisms that regulate their function and maintenance remain incompletely understood. Further, SSC function and fertility can be compromised by exposure to genotoxic drugs but cellular pathways mediating the regenerative response of SSCs following germline damage are poorly studied. Our recent studies have focused on understanding the distinct roles played by growth factor-regulated signalling pathways in controlling SSC dynamics and function under homeostatic and regenerative conditions through use of mouse models and single cell approaches. We find that SSCs mediating germline regeneration adopt a unique cellular state associated with alterations in PI3K-mTORC1 signalling when compared to SSCs of steady-state tissue. Moreover, while chronic stimulation of PI3K-mTORC1 signalling is detrimental to SSC maintenance in undisturbed tissue, transient activation of this pathway is required to promote the SSC regenerative response. Importantly, concerted inhibition of growth factor signalling, including the PI3K-mTORC1 pathway, in SSCs results in pronounced defects in germline recovery after damage. In addition, the transcription factor and cell cycle regulator FOXM1 was found to integrate diverse signalling inputs to support SSC regenerative capacity. Combined, our data demonstrate key instructive roles for microenvironmental growth factors and PI3K-mTORC1 signalling in defining distinct functional states of homeostatic and regenerative SSCs.