Molecular magnetic resonance imaging (MRI) provides information non-invasively at cellular and molecular levels, for both early diagnosis and monitoring therapeutic follow-up. This imaging technique requires the development of a new class of contrast agents, which signal changes (typically becomes enhanced) when in presence of the cellular or molecular process to be evaluated. Even if molecular MRI has had a prominent role in the advances in medicine over the past two decades, the large majority of the developed probes to date are still in preclinical level, or eventually in phase I or II clinical trials. The development of novel imaging probes is an emergent active research domain. This review focuses on gadolinium-based specific-targeted contrast agents, providing rational design considerations and examples of the strategies recently reported in the literature.