Health reform requires safety net settings to transform care delivery, but how they will innovate in order to achieve this transformation is unknown. Two series of key informant interviews (N = 28) were conducted in 2012 with leadership from both California's public hospital systems and community health centers. Interviews focused on how innovation was conceptualized and solicited examples of successful innovations. In contrast to disruptive innovation, interviewees often defined innovation as improving implementation, making incremental changes, and promoting integration. Many leaders gave examples of existing innovative practices to meeting their diverse patient needs, such as patient-centered approaches. Participants expressed challenges to adapting quickly, but a desire to partner together. Safety net systems have already begun implementing innovative practices supporting their key priority areas. However, more support is needed, specifically to accelerate the change needed to succeed under health reform.