It has been recently proposed that Flory-Huggins theory (FH), which finds widespread use in the polymer community, be applied to understand the partitioning of relatively short alkane chains between an organic phase and water. Use of this theory, which predicts that the molar volumes of the different species play an important role in determining solubility, results in a significant increase in the hydrophobic surface tension estimated from transfer experiments. However, the application of FH theory to the analysis of alkane solubility has been widely criticized. Here, we derive this theory accounting specifically for the pressure of the lattice system, and show that it is appropriate for transfers from a condensed polymer solvent phase to either a gas phase or a monomer solvent. The sweeping criticisms of the applicability of FH theory to partition experiments that have appeared in the recent literature are therefore not valid. A new result is that FH theory is valid for treating partition data for solutes of arbitrary shape, as long as the solvent is chain-like. On the other hand, Monte Carlo simulations using the chain increment method indicate that Flory-Huggins theory overestimates molecular size effects by 25% even in the case of athermal lattice systems, indicating that the predictions of this theory should be viewed as first-order estimates of true size effects. The physical origins of Flory-Huggins theory are discussed, and connections are made to Hildebrand’s free volume theory and also to Sharp et al.’s ideal gas derivation of volume effects. The role of molar volume effects in transfers of solutes from a gas phase to monomer solution are also considered.