This chapter looks at the issue of homelessness from a social and health perspective in the conditions of the Pilsen Region. The introductory part is prepared on the basis of obtaining relevant knowledge gained by studying both domestic and foreign literature, where attention is paid to all aspects of the studied issue related to homelessness (defining key terms, typology of homelessness, causes of homelessness, legislative minimum related to the issue) as well as the consequences of homelessness and health and social risks associated with homelessness. A qualitative research method was used for data collection and subsequent in-depth analysis. Specifically, it was structured interviews, where the criterion for inclusion of respondents in the research sample was homelessness and simultaneous residence in the Pilsen Region. Furthermore, a retrospective observational study was conducted by analysing the internal, exclusively electronic medical records of the Emergency Rescue Service of the Pilsen Region over the last five years. From the total sample of calls of each call-out group, only those records that were made to homeless persons were examined. From this group of calls, calls to persons who fulfilled the criterion of homelessness were detected and at least five calls of individual call groups of the Emergency Rescue Service of the Pilsen Region to these persons were carried out in the monitored period (last 5 years). From the specific cases, summary tables were created indicating the classification, specification and subsequent placement of the specific affected person in a health facility.