The success of highly target-conformal treatments such as intensity-modulated radiotherapy (IMRT) can be compromised by motion of the inner organs and random patient setup errors. This article gives an overview of different studies that looked at the effect of organ motion and setup errors on radiation therapy dose distributions, both from a qualitative and quantitative point of view. The qualitative findings are generally applicable (ie, case independent). It is found that motion always leads to a blurring of the dose distribution. In addition, there are so-called interplay effects if the treatment delivery involves moving parts, such as multileaf collimators. After a large number of fractions, the interplay effects lead to a normal distribution of the dose value around the average blurred value. Thirdly, organ motion can also cause a spatial deformation of the dose distribution. Quantitatively it has been found that both deformation and interplay effects appear to be small (in the order of 1%-2%) in many typical clinical cases. The dominant effect is the blurring of the dose distribution, which is, in essence, independent of the treatment technique, and is not more pronounced in IMRT than in more conventional treatment techniques. However, because in IMRT there is a tendency to reduce or compromise target margins, the blurring has potentially a bigger effect on the outcome of IMRT, unless precision dose delivery techniques (such as gated or motion-synchronized beams) are used. An alternative to the use of margins is to do the planning based on blurred dose distributions.