In this mini-review, we highlight selected research by the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence “Precision Medicine in Chronic Inflammation” focusing on clinical sequencing and the clinical utility of polygenic risk scores as well as its implication on precision medicine in the field of the inflammatory diseases inflammatory bowel disease, atopic dermatitis and coronary artery disease. Additionally, we highlight current developments and discuss challenges to be faced in the future. Exemplary, we point to residual challenges in detecting disease-relevant variants resulting from difficulties in the interpretation of candidate variants and their potential interactions. While polygenic risk scores represent promising tools for the stratification of patient groups, currently, polygenic risk scores are not accurate enough for clinical setting. Precision medicine, incorporating additional data from genomics, transcriptomics and proteomics experiments, may enable the identification of distinct disease pathogeneses. In the future, data-intensive biomedical innovation will hopefully lead to improved patient stratification for personalized medicine.