Immune checkpoint blockade (ICB) improves outcomes for some patients with advanced or metastatic cancers. Despite demonstrable progress, many patients do not respond to ICB. Recently, clinical trials have focused on combinations of ICB with radiation therapy. Although two recent Phase III randomized trials demonstrated improved survival with adjuvant ICB following chemoradiation, other Phase I/II/III trials are either negative or inconclusive, but do yield suggestive results and promising insights into future therapeutic strategies. We provide a selective review of a subset of these trials and attempt to integrate with basic laboratory findings where relevant to define issues pertaining to the combination of radiotherapy and immunotherapy.