ObjectiveTo review and synthesise qualitative studies that have explored subjective experiences of people with lived experience of mental health-related illness/crisis (MHC), their families and first responders.DesignA systematic review of qualitative evidence was conducted. English-language articles exploring the content of interactions and participants’ experiences were included.Data sourcesMEDLINE, PsycINFO, EMBASE, CINAHL; Google Scholar, SAGE journals, Science Direct and PubMed.Data extraction and synthesisTwo reviewers read and systematically extracted data from the included papers. Papers were appraised for methodological rigour using the Critical Appraisal Skills Programme Qualitative Checklist. Data were thematically analysed.ResultsWe identified 3483 unique records, 404 full-texts were assessed against the inclusion criteria and 79 studies were included in the qualitative synthesis. First responders (FRs) identified in studies were police and ambulance staff. Main factors influencing response are persistent stigmatised attitudes among FRs, arbitrary training and the triadic interactions between FRs, people with mental illness and third parties present at the crisis. In addition, FR personal experience of mental illness and focused training can help create a more empathetic response, however lack of resources in mental health services continues to be a barrier where ‘frequent attenders’ are repeatedly let down by mental health services.ConclusionLack of resources in mental healthcare and rise in mental illness suggest that FR response to MHC is inevitable. Inconsistent training, complexity of procedures and persistent stigmatisation make this a very challenging task. Improving communication with family carers and colleagues could make a difference. Broader issues of legitimacy and procedural barriers should be considered in order to reduce criminalisation and ensure an empathetic response.