While we acknowledge that many findings from in vitro studies of MYC-driven cancer metabolism hold true in vivo (Wahlström and Henriksson, 2015; Stine et al., 2015), we will discuss here the various models used to study the regulation of cancer metabolism by MYC in vivo (summarized in Table 1), and provide broader context on some of the questions that remain to be answered. Here, MYC is linked to cancer.