Most microbes on earth, whether they live in the ocean, the soil or in animals, are not growing fast, but instead struggling to survive. Some genes and environmental conditions affecting starvation survival have been identified, but despite almost a century of study, we do not know which processes lead to irreversible loss of viability, which maintenance processes counteract them and how lifespan is determined from the balance of these opposing processes. We found that a lack of nutrients results in the collapse of ion homeostasis, triggering a positive-feedback cascade of osmotic swelling and membrane permeabilization that ultimately results in lysis. Based on these findings, we showed that ion transport is the major energetic requirement for starving cells and the primary determinant of cell death. We developed a simple mathematical model that integrates ion homeostasis and nutrient recycling to predict death rate under diverse conditions, such as changes of cell size, medium composition, and prior growth conditions. Guided by model predictions, we found that cell death during starvation could be rescued by replacing inorganic ions from the medium with a non-permeating osmo-protectant, removing the cost of ion homeostasis.