  In inflationary models that produce a spike of power on short scales,
back-reaction of small-scale substructure onto large-scale modes is enhanced.
We argue that the separate universe framework provides a highly convenient tool
to compute loop corrections that quantify this back-reaction. Each loop of
interest is characterized by large hierarchies in wavenumber and horizon exit
time. The separate universe framework highlights important factorizations
involving these hierarchies. We interpret each loop correction in terms of a
simple, classical, back-reaction model, and clarify the meaning of the
different volume scalings that have been reported in the literature. We argue
that significant back-reaction requires both short-scale nonlinearities and
long-short couplings that modulate the short-scale power spectrum. In the
absence of long-short couplings, only incoherent shot noise-like effects are
present, which are volume-suppressed. Dropping the shot noise, back-reaction
from a particular scale is controlled by a product of $f_{NL}$-like parameters:
an equilateral configuration measuring the nonlinearity of the short-scale
modes, and a squeezed configuration measuring the long-short coupling. These
may carry important scale dependence controlling the behaviour of the loop in
the decoupling limit where the hierarchy of scales becomes large. In
single-field models the long-short coupling may be suppressed by this
hierarchy, in which case the net back-reaction would be safely suppressed. We
illustrate our framework using explicit computations in a 3-phase
ultra-slow-roll scenario. Finally, we discuss different choices for the
smoothing scale used in the separate universe framework and argue the effect
can be absorbed into a renormalization of local operators.
