Responding to alarm systems which usually commit a number of false alarms and/or misses involves decision-making under uncertainty. Four laboratory experiments including a total of 256 participants were conducted to gain comprehensive insight into humans' dealing with this uncertainty. Specifically, it was investigated how responses to alarms/non-alarms are affected by the predictive validities of these events, and to what extent response strategies depend on whether or not the validity of alarms/non-alarms can be cross-checked against other data. Among others, the results suggest that, without cross-check possibility (experiment 1), low levels of predictive validity of alarms ( ≤ 0.5) led most participants to use one of two different strategies which both involved non-responding to a significant number of alarms (cry-wolf effect). Yet, providing access to alarm validity information reduced this effect dramatically (experiment 2). This latter result emerged independent of the effort needed for cross-checkings of alarms (experiment 3), but was affected by the workload imposed by concurrent tasks (experiment 4). Theoretical and practical consequences of these results for decision-making and response selection in interaction with alarm systems, as well as the design of effective alarm systems, are discussed.