The cortex is the outermost region of the cell, comprising all of the elements from the plasma membrane to the cortical actin cytoskeleton that cooperate to maintain the cell’s shape and topology. In eukaryotes without cell walls, this cortex governs the contact between their plasma membranes and the environment and thereby influences cell shape, motility, and signaling. It is therefore of considerable interest to understand how cells control their cortices, both globally and with respect to small sub-domains. Here we review the current understanding of this control, including the regulation of cell shape by balances of outward hydrostatic pressure and cortical tension. The actomyosin cytoskeleton is the canonical regulator of cortical rigidity and indeed many would consider the cortex to comprise the actin cortex nearly exclusively. However, this actomyosin array is intimately linked to the membrane, for example via ERM and PIP2 proteins. Additionally, the lipid membrane likely undergoes rigidification by other players, such as BAR proteins. Recent data also indicates that the septin cytoskeleton may play a formidable and more direct role in stabilization of membranes, particularly in contexts where cells receive limited external stabilization from their environments. Here, we review how septins may play this role, drawing on their physical form, their ability to directly bind and modify membranes and actomyosin, and their interactions with vesicular machinery. Deficiencies and alterations in the nature of the septin cytoskeleton may thus be relevant in multiple disease settings.