The chemical analysis of paintings provides a unique opportunity for problem-based learning in the instrumental analysis laboratory. The important concepts of sampling, sample handling, sample preparation, and choice of instrumental method are required to be able to effectively work with art samples. Additionally, the chemical analysis of these samples also brings in fields of proteomics (binder analysis) and nanocomposites or nanotechnology (heterogeneity in the paint structure) which are concepts that students have a great interest in since they hear about these terms quite often. The PBL approach piques student interest in the material. However, instructors should be aware that a successful PBL-approach requires an extensive amount of planning and preparation. My experience has been that using the PBL-approach was worth the effort since it provided an intellectually challenging chemical analysis problem and for some students it was their first real positive research experience.