Background: Systemic and structural issues of rapid response system (RRS) models can hinder implementation. This study sought to understand the ways in which acute care clinicians (physicians and nurses) experience and negotiate care for deteriorating patients within the RRS. Methods: Physicians and nurses working within an Australian academic health centre within a jurisdictional-based model of clinical governance participated in focus group interviews. Verbatim transcripts were analysed using thematic content analysis. Results: Thirty-four participants (21 physicians and 13 registered nurses [RNs]) participated in six focus groups over five weeks in 2014. Implementing the RRS in daily practice was a process of informal communication and negotiation in spite of standardised protocols. Themes highlighted several systems or organisational-level barriers to an effective RRS, including (1) responsibility is inversely proportional to clinical experience; (2) actions around system flexibility contribute to deviation from protocol; (3) misdistribution of resources leads to perceptions of inadequate staffing levels inhibiting full optimisation of the RRS; and (4) poor communication and documentation of RRS increases clinician workloads. Conclusion: Implementing a RRS is complex and multifactorial, influenced by various inter- and intra-professional factors, staffing models and organisational culture. The RRS is not a static model; it is both reflexive and iterative, perpetually transforming to meet healthcare consumer and provider demands and local unit contexts and needs. Requiring more than just a strong initial implementation phase, new models of care such as a RRS demand good governance processes, ongoing support and regular evaluation and refinement. Cultural, organizational and professional factors, as well as systems-based processes, require consideration if RRSs are to achieve their intended outcomes in dynamic healthcare settings.