How do you handle a ComboBox SelectionChanged in MVVM?

This post is quite old, but since I got the same issue. Here is how I solved it (using framework 4.0) : the idea is to use System.Windows.Interactivity.

In the XAML :

<ComboBox ItemsSource="{Binding Items}">
    <i:Interaction.Triggers>
        <i:EventTrigger EventName="SelectionChanged">
            <i:InvokeCommandAction Command="{Binding SelectionChangedCommand}"/>
        </i:EventTrigger>
    </i:Interaction.Triggers>
</ComboBox>

Then you just need to implement the SelectionChangedCommand in your viewmodel.