Compared with giving immunotherapy in the adjuvant (post-operative) setting, administering immunotherapy pre-operatively (neoadjuvant immunotherapy) may have additional benefits for patients with operable cancers including de-escalating therapy and improving outcomes. I will discuss the immunological rationale for this approach and key pre-clinical data. Next, I will briefly overview the current state of play for neoadjuvant immunotherapy trials in various cancer types, including the mechanistic correlates of effective neoadjuvant immunotherapy that have been reported thus far. Finally, I will discuss future directions for the field and a personal reflection of the complexities and benefits of the neoadjuvant approach for investigator-initiated trials of immunotherapy.