The literature on skill-biased technical change has examined the role of skills in the adoption of new technology. Here the focus is on the creation of new technology, that is, innovation. Low skill firms are hypothesized to benefit less from innovation activities, particularly collaborative research and development (R&D). In other words, skills and innovation are complementary. Complementarities associated with innovation may generate persistent differences in firm behavior and performance. Results from a panel of manufacturing firms indicate that technical skills reinforce the profitability effects of innovation and R&D collaboration. Skills, collaboration, and innovation form a system of interdependent activities.