  In this work we provide a comprehensive analysis of the activation problem
out of equilibrium. We generalize the Arrhenius law for systems driven by non
conservative time independent forces, subjected to retarded friction and
non-Markovian noise. The role of the energy function is now played by the out
of equilibrium potential {\phi} = -lim_{T{\to}0} T log P_s, with P_s being the
steady state probability distribution and T the strength of the noise. We
unveil the relationship between the generalized Arrhenius law and a
time-reversal transformation discussed in the context of fluctuations theorems
out of equilibrium. Moreover, we characterize the noise-activated trajectories
by obtaining their explicit expressions and identifying their irreversible
nature. Finally, we discuss a real biological application that illustrates our
results.
