The implementation of Team-Based Learning (TBL, http://www.teambasedlearning.org) in one-semester undergraduate courses of chemistry offered to first year students is reported. TBL is an active learning instructional strategy heavily relying on small group interaction. Teaching lab classes in a TBL context presented a specific challenge, as decisions were required about their role in the global framework and the possibility of incorporating lab activities as “teamwork”. The design of lab sessions as TBL team application activities is here also illustrated, both for a course of General Chemistry and a course of Organic Chemistry. TBL dramatically improved students class attendance and participation. Its implementation has provided a unique opportunity for the pedagogical development of teaching staff. A moderate number of students reported discomfort with TBL: the requirement of individual preparation before classes and the impact of team participation in the final grade is indeed a new ground for most students, often perceived as a troubling deviation from the common social paradigm of the learning process. The role of the instructor as a facilitator of individual and team work, and the clear explanation of the method are thus of utmost relevance.