In this article, we review the challenges and opportunities related to developing effective, collaborative relationships between primary care and oncology providers during the initial cancer treatment period. This point in the cancer care continuum is complex and often represents the first major transition in care between primary care providers and oncology specialists. Patients often receive care from multiple providers in a number of different settings and are faced with making treatment decisions in a short, concentrated period of time. Patients consistently report having significant informational and emotional needs that are often unmet during this period. Using the published literature, we have identified a number of challenges during this part of the treatment continuum that may limit providers' ability to deliver effective care, including provider care discontinuities, information exchange problems, and gaps in provider role clarity that may be especially problematic within the context of managing comorbid health conditions. The limited published literature specific to this step in the cancer care trajectory supports the importance of ongoing primary care-specialist collaboration during this phase in the care continuum for both medical and psychosocial care. How to best achieve effective collaboration between providers requires further research in information exchange and tools to support it, evaluation of shared care models specific to the cancer context, and studies of the potential role of multidisciplinary case conferencing that include the primary care provider.