To incorporate an active learning component in a one-semester biochemistry course, students were asked to create crossword puzzles using key concepts. Student observations on the use of self-made crossword puzzles as an active-learning instructional tool were collected using a 5-point Likert survey at the end of the semester. A majority of the students felt that the crossword puzzles enhanced their learning of biochemical concepts. Constructing their own crosswords contributed to a positive experience by allowing the students to better engage in the learning experience. In addition, multiple-choice questions using clues from the crossword puzzles were also incorporated into the final examinations. Therefore, self-made crossword puzzles offer a simple and creative way to incorporate active learning into a number of courses in the biochemistry curriculum. (Contains 1 table and 2 figures.)