Despite considerable advancements that shattered previously held dogmas about the metastatic cascade, the evolution of therapies to treat metastatic disease has not kept up. In this Opinion article, I argue that, rather than waiting for metastases to emerge before initiating treatment, it would be more effective to target metastatic seeds before they sprout. Specifically, I advocate directing therapies towards the niches that harbour dormant disseminated tumour cells to sensitize them to cytotoxic agents. Treatment sensitization, achieved by disrupting reservoirs of leukaemic stem cells and latent HIV, argues that this approach, although unconventional, could succeed in improving patient survival by delaying or even preventing metastasis.