Epilepsy is a disease characterized by recurrent seizures. When focal in onset, these events start in a defined location and then spread through short- and long-range connections to local and widespread interconnected brain networks. Recent advances in neuroimaging of activity-dependent fluorophores have made widefield imaging an ideal tool for tracking the neural dynamics underlying the onset and propagation of seizures. Here we describe the methods and experimental techniques that can be employed to study seizures in awake behaving rodents, with a particular focus on simultaneously applying genetically encoded calcium indicators and hemodynamic imaging. These methods can be easily extended to normal brain mechanisms in healthy brain as well as other neurological diseases.