Deprivation or restricted access to either food or fluids is a common research procedure in laboratory animals. The purpose of the present review is to present and summarize some of the important physiologic effects of such procedures and to assess their effect on the well-being of the animal. This assessment is presented within a context of the typical research objectives of such procedures. Specific suggestions are made that are intended to strike a balance between meeting these research objectives and ensuring the physiologic and behavioral welfare of the animals under study. Most of the information presented is specifically related to rats and mice but, with appropriate adjustments, the principles likely will generalize to other laboratory species. I present evidence that after 12 to 24 h without access, animals efficiently reduce further fluid or energy losses by a combination of behavioral and physiologic adjustments. These adjustments likely minimize the additional physiologic or psychologic stress of deprivation. Animals have endogenous nycthemeral rhythms that make them particularly adaptable to once-daily occurrences, such as food or water access. Longer periods of acute deprivation or chronic restriction are acceptable procedures, but only with suitable monitoring protocols, such as routine weighing and target weights. In the case of chronic food restriction, the use of species-, age-, and strain-specific target growth rates is more appropriate than using a fraction of age-matched free-fed animal weights as a target.