Exhaled breath analysis of volatile organic compounds (VOCs) has emerged as a promising non-invasive approach for clinical diagnostics, as breath VOCs can reflect disease-associated metabolic, inflammatory, and microbiological changes. For the reason, VOC-based diagnostics have been explored in a wide range of clinical settings, with vigorous research in cancer, infectious diseases, and respiratory diseases. However, differences in breath sampling, analytical platforms, and data processing strategies have limited comparability across studies and hindered robust clinical translation. In this review, we summarize clinical studies applying exhaled VOC analysis for disease diagnostics, organized by major disease groups, and compare analytical techniques, diagnostic performance, and key limitations. In cancer research, distinct VOC patterns have been reported across various cancer types, with lung cancer being the most extensively investigated. In infectious diseases, studies have mainly focused on viral respiratory infections and pneumonia, reporting VOC profiles associated with specific pathogens and host immune responses. In respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma, VOC signatures have been linked to inflammatory status and disease activity. This paper highlights current achievements and shared methodological limitations in breath VOC research and emphasizes the need for standardized protocols and large-scale validation to facilitate routine clinical application.