The current understanding of the principles underlying particle therapy conCentreates on protons and carbon ions, but is seriously deficient for all other ions and may thus subvert the enormous potential of these modalities. The limitations include: (1) Uncertainties in the relative biological effectiveness (RBE). (estimated about 25% in maximum RBE for He-ions). (2) Projectile fragmentation and nuclear reactions produce significant out of field dose, which may lead to toxicities and radiation-induced second malignancies. (3) Biological effects data are sparse and lack significantly in precision. The vast majority of published studies are associated with considerable systematic uncertainties in LET determinations. While there exist significant amounts of data concerning Chinese hamster cells, systematic and comprehensive research of human cancer and normal tissue cell lines needs to be conducted. (4) Ion beams are subject to angular and range straggling, leading to varying magnitudes of penumbrae and degraded distal falloffs.