We present a new approach for estimating the 3.6 micron stellar mass-to-light ratio in terms of the [3.6]-[4.5] colors of old stellar populations. Our approach avoids several of the largest sources of uncertainty in existing techniques. By focusing on mid-IR wavelengths, we gain a virtually dust extinction-free tracer of the old stars, avoiding the need to adopt a dust model to correctly interpret optical or optical/NIR colors normally leveraged to assign M/L. By calibrating a new relation between NIR and mid-IR colors of GLIMPSE giant stars we also avoid discrepancies in model predictions for the [3.6]-[4.5] colors of old stellar populations due to uncertainties in molecular line opacities. We find that the [3.6]-[4.5] color, which is driven primarily by metallicity, provides a tight constraint on M/L_3.6, which varies intrinsically less than at optical wavelengths. The uncertainty on M/L_3.6 of ~0.07 dex due to unconstrained age variations marks a significant improvement on existing techniques for estimating the stellar M/L with shorter wavelength data. A single M/L_3.6=0.6 (assuming a Chabrier IMF), independent of [3.6]-[4.5] color, is also feasible as it can be applied simultaneously to old, metal-rich and young, metal-poor populations, and still with comparable (or better) accuracy (~0.1 dex) as alternatives. We expect our M/L_3.6 to be optimal for mapping the stellar mass distributions in S4G galaxies, for which we have developed an Independent Component Analysis technique to first isolate the old stellar light at 3.6 micron from non-stellar emission (e.g. hot dust and the 3.3 PAH feature). Our estimate can also be used to determine the fractional contribution of non-stellar emission to global (rest-frame) 3.6 micron fluxes, e.g. in WISE imaging, and establishes a reliable basis for exploring variations in the stellar IMF.
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