  The interface between hemoglobin (Hb) and its environment, in particular
water, is of great physiological relevance. Here, results from {\it in vitro},
{\it in vivo}, and computational experiments (molecular dynamics simulations)
are summarized and put into perspective. One of the main findings from the
computations is that the stability of the deoxy, ligand-free T-state (T$_0$)
can be stabilized relative to the deoxy R-state (R$_0$) only in sufficiently
large simulation boxes for the hydrophobic effect to manifest itself. This
effect directly influences protein stability and is operative also under
physiological conditions. Furthermore, molecular simulations provide a
dynamical interpretation of the Perutz model for Hb function. Results from
experiments using higher protein concentrations and realistic cellular
environments are also discussed. One of the next great challenges for
computational studies, which as we show is likely to be taken up in the near
future, is to provide molecular-level understanding of the dynamics of proteins
in such crowded environments.
