The essential function of the COG complex has been proposed to depend not only upon SNAREs interactions, but also interactions with Rabs (Miller et al., 2013; Willett et al., 2013a; Figure 1). Within this context, Rabs are believed to act as molecular switches that cycle between GDP-bound (inactive) and GTP-bound (active) states and regulate cargo trafficking by acting in an intracellular compartment-specific manner. Active (GTP-bound) Rabs regulate trafficking by binding effector molecules like tethering factors and motor proteins (D'Adamo et al., 2014). Binding to some effectors leads to the activation of other Rabs, in a sequence known as the Rab Cascade (Pfeffer, 2013). Nine distinct, Golgi-localized Rabs are known to interact with COG (Miller et al., 2013; Willett et al., 2013b, 2014). The compartment-specific nature of these different Rabs makes them a potential landmark for COG membrane localization and interaction. As with the SNAREs, this review will limit the discussion to COG partners Rab1a, Rab1b, Rab2, Rab4a, and Rab6a that are implicated in neuronal abnormalities (Table 1).