Nuclear medicine plays an increasingly important role in several neoplasms management through a theragnostic approach by which targeted molecular imaging and radiotherapy are obtained with the use of radionuclide pairs with similar characteristics. In some cases, nuclear theragnostic use a pair of agents with identical chemical and biological characteristics while in others are employed theragnostic molecules which are not chemically or biologically identical but show similar biodistribution (so-called "twins in spirit" radiopharmaceuticals). This strategy was developed for the first time over 75 years ago, when iodine-131 was used for diagnostic imaging, confirmation of target expression and radionuclide therapy of thyroid cancer. Other theragnostic approaches were subsequently introduced with significant clinical results and some of them are currently considered standard treatment for different cancers. However, as any other therapy, also nuclear theragnostic treatment carries the potential risk of early deterministic and late stochastic off-target adverse effects, generally minimal and easily managed. This article reviews the reported side effects and risks of the main radiopharmaceuticals used for nuclear theragnostic in oncology for the treatment of thyroid cancer, neuroendocrine neoplasms, adrenergic tumors, metastatic prostate cancer, and liver tumors. Selecting appropriate patients using a multidisciplinary approach, meticulous pretreatment planning and knowledge of methods permit to decrease the incidence of these potential side effects.