Angiogenesis, the formation of new blood vessels, is a popular target of various therapies. Some therapies, like those used in tissue engineering, are designed to promote angiogenesis and new tissue growth, while other therapies, such as those designed to fight cancer, aim to suppress angiogenesis— a lifeline for tumor cells. Unfortunately, these therapies aren’t always effective. Now, a new mathematical model could help researchers understand what molecular levers to pull to effectively modulate angiogenesis. Trained on published experimental data, the model predicted the effects of activating two common targets of angiogenesis-based therapies: vascular endothelial growth factor, or VEGF, and fibroblast growth factor, or FGF. Computational experiments showed that the two factors modify both the ERK signaling pathway, which is linked to cell proliferation, and the Akt signaling pathway, which is associated with cell survival and migration. The ERK pathway was more sensitive to changes in VEGF and FGF, with simultaneous activation of VEGF and FGF exerting the strongest effects. While more work is needed before the results of the computational model can be generalized, the findings could help researchers develop more effective angiogenesis-based therapies.