A variety of methods and arrangements for detecting misfire in a skip fire engine control system are described. In one aspect, a window is assigned to a target firing opportunity for a target working chamber. A change in an engine parameter is measured during the window. A determination is made as to whether a firing opportunity before the target firing opportunity is a skip or a fire and/or whether a firing opportunity after the target firing opportunity is a skip or a fire. Based at least in part on this skip/fire determination, a determination is made as to whether the target working chamber has misfired. In various embodiments, if the target working chamber is identified as persistently misfiring, the firing sequence is modified so that the target working chamber is deactivated and excluded from the firing sequence. In still other embodiments, a torque model is used to detect engine-related problems.