A computational protocol is employed to glean new insight into the kinetics of several 1,5-hydrogen atom (H) shift reactions subsequent to first- and second-generation OH/O-2 additions to isoprene. The M06-2X density functional was initially used with the Nudged Elastic Band (NEB) method to determine the potential energy surface of OH/O-2 addition reactions, the 1,5-H shift reactions, and the fragmentation exit channels. The Master Equation Solver for Multi-Energy Well Reactions (MESMER) was applied to determine the rate constants for OH addition and the 1,5-H shifts. M06-2X was capable of quantifying the rate constants of OH addition to the first and second double bonds of isoprene with deviations less than 17% from the experimentally determined values. However, M06-2X underestimated the 1,5-H shift rate constants of second-generation isoprene peroxy radicals. Consequently, MN15, omega B97X-D, and CBS-QB3 methods were employed to compute average barrier heights to first- and second-generation 1,5-H shifts. In the first generation, the rate constants of H abstraction by beta(1,2) and (4,3) isoprene hydroxy-peroxy radicals from the neighboring hydroxyl group are 1.1 X 10(-3) and 2.4 X 10(-3)s(-1), respectively. These values are determined primarily by the barrier of the H shift reaction and, to a smaller albeit nonnegligible extent, by the stability of the resulting alkoxy radical and the exit barrier leading to C-C bond dissociation. In contrast, the average second-generation rate constant of 1,5-H shifts from H-R-OH sites to the peroxy radical is 1.8 X 10(-1)s(-1), with tunneling playing the significant role of increasing this value relative to first-generation 1,5-H shifts. Under low NOx conditions, first-generation isoprene oxidation reactions may recycle HOx at levels ranging from 10 to 30% due in large part to 1,5-H shifts, with the recycling efficiency being sensitive to HO2 concentrations and temperature. HOx recycling is expected to increase to levels beyond 80% in second-generation reactions of oxidized isoprene species because of isoprene epoxydiol (IEPDX) formation and further 1,5-H shifts that are kinetically favorable.