A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer.