In this study we explored predictors and moderators of response to Internet-based cognitive behavioral therapy (CBT) and Internet-based problem-solving therapy (PST) for depressive symptoms. The sample consisted of 263 participants with moderate to severe depressive symptoms. Of those, 88 were randomized to CBT, 88 to PST and 87 to a waiting list control condition. Outcomes were improvement and clinically significant change in depressive symptoms after 8 weeks. Higher baseline depression and higher education predicted improvement, while higher education, less avoidance behavior and decreased rational problem-solving skills predicted clinically significant change across all groups. No variables were found that differentially predicted outcome between Internet-based CBT and Internet-based PST. More research is needed with sufficient power to investigate predictors and moderators of response to reveal for whom Internet-based therapy is best suited.