WPF

private void Cmd_CloseDir_Executed(object sender, ExecutedRoutedEventArgs e)
{
  SetUiAsBusy();
  if (MessageBox.Show(this, "Do you really...", "Confirm close", MessageBoxButton.YesNo) == MessageBoxResult.Yes)
  {
    DirTreeNode theDirTreeNodeToRemove = MainTree_GetSelectedDirTreeNode();
    MasterList.RemoveDirTreeNodeAndChildren(theDirTreeNodeToRemove, true);
    MasterList.FillUniqueLists();
    MasterList.FileMatches.Clear();
  }
  SetUiAsFree();
}

private void SetUiAsBusy()
{
  MasterList.UiIsFree = false;
  NotifyPropertyChanged_All();
  CommandManager.InvalidateRequerySuggested();
}

public class MyApp : Application
{
  private static bool newMutex;
  public static void Main()
  {
    using (Mutex m = new Mutex(true, "myApplication", out newMutex))
    {
      if (!mutexIsNew)
        // Shut it down
    }
  }
}

public partial class App : Application
{
    private static bool mutexIsNew;

    public App() : base()
    {
        using (Mutex m = new Mutex(true, "MyApp", out mutexIsNew))
        {
            if (mutexIsNew)
            {
                AppMainWindow mainwindow = new AppMainWindow();
                mainwindow.Show();
            }
            else
            {
                App.Current.Shutdown();
            }
        }
    }
}

Jammer

Going where everyone here has gone before!
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using System;
using System.Collections.Generic;
using System.Linq;
using System.Text;
using System.Windows;
using System.Threading;

namespace SingleInstanceApp
{
  public class SIApplication : Application
  {
    private static bool isNew;
    [STAThread]
    public static void Main()
    {
      using (Mutex m = new Mutex(true, "SIApplication.Mutex", out isNew))
      {
        if (isNew)
        {
          SIApplication app = new SIApplication();
          app.InitializeComponent();
          app.Run();
        }
      }
    }

    public void InitializeComponent()
    {
      this.StartupUri = new Uri("Window1.xaml", System.UriKind.Relative);
    }
  }
}

<br />
public partial class App : Application<br />
{<br />
    protected override void OnStartup(StartupEventArgs e)<br />
    {<br />
        bool mutexCreated;<br />
        mutexRunOnce = new System.Threading.Mutex(<br />
            true, "{someGUID}", out mutexCreated);<br />
        if (!mutexCreated)<br />
        {<br />
            return;<br />
        }<br />
<br />
        base.OnStartup(e);<br />
    }<br />
    //...<br />
}<br />